This is a competing renewal of the UCSD HIV Neurobehavioral Research Center (HNRC), in response to PAR-08-009. The renewal builds on the track record of the HNRC as a national and international leader and resource facilitating research on neuropathogenesis, treatment, and prevention of HIV-associated neurocognitive disorders (HAND). In the renewal, our work will be guided by continuity of the major themes established in the prior period, and augmented by three areas of special concentration in the next 5 years. The continuity themes include: 1) delineating the attributes of the virus, host, and host-virus interaction that determine HAND; 2) identifying mechanisms by which host-virus factors generate neural injury; 3) understanding the role of comorbid factors; 4) developing strategies to prevent or ameliorate HAND; 5) determining the real life significance of HAND and its treatment. The areas of special emphasis will be 1) supporting studies examining the effects of aging on the prevalence, manifestations, mechanisms, and treatment of HAND; 2) determining the incidence of HAND, its clinical and biological correlates, unique mechanisms, and possibility of prevention in the acute/early stages of HIV infection (i.e., in the first 6 months); and 3) implementing improved translation of research findings to the clinic. In terms of the latter, the HNRC envisions support of studies on better CNS penetrating ARVs, adjunctive neuroprotective therapies, improved biomarkers of HAND, and improved assessment methodologies derived from research experience. To accomplish these goals the HNRC will maintain 5 scientific Cores (Neuromedical, Neurobehavioral, Neurolmaging, Neurovirology, and Neurobiology) that will provide intellectual leadership and technical support, plus 3 over-arching cores to support and coordinate their activities: The Developmental Core will support innovative preliminary experiments and coordinate training and mentorship with the scientific cores and HNRC associated faculty, targeting the future generation of neuro-HIV scientists. The International Core will provide consultation to international scholars, translation of techniques developed at the HNRC to diverse settings around the world, and support joint research efforts between US and foreign investigators. The activities of the HNRC will be led by an Executive Team and synergized by a Coordinating Core consisting of Administrative, Participant Accrual and Retention, Data Management and Information Systems, and Statistics units. With these structures and processes the HNRC will continue to foster its national and international leadership role in neuro-HIV research, training, and treatment.